9 - Metabolism of Bone

Biochemical Markers of Bone Metabolism

Key Points

The plasma concentration of calcium, phosphate and

magnesium is dependent upon bone mineral
absorption, resorption, intestinal absorption and
renal excretion.

Regulating hormones are PTH, calcitonin and 1,25dihydroxyvitamin D

80% of hypercalcemia is due to primary

hyperparathyroidism (elevated PTH) or malignancy
(decreased PTH)

Hypocalcemia is due to chronic renal failure and

many others (acute pancreatitis)

Bio-intact PTH measures biologically active PTH;

useful in patients with impaired renal functions and in
surgical resection of parathyroid adenoma

Osteoporosis is the most common metabolic disease

of the bone
Osteomalacia is a failure to mineralize newly formed

osteoid in the mature skeleton

Bone

Inorganic minerals= calcium and phosphorus

Organic matrix = 90-95% type 1 collagen, 5-10% noncollagenous proteins osteocalcin, osteopontin,
thrombospondin, sialoproteins
Cells= osteoblast, osteoclast, osteocyte
Compact bone:
75% matrix, 25% air spaces

Cancellous bone:
95% air spaces, 5% matrix

Calcium

Distribution, function, homeostasis: 99% in the

skeleton, needed for coagulation, contractility,
enzymatic, integrity of cell membrane.
Analytical techniques: colorimetric, atomic absorption
spectrophotometry (most accurate), indirect
potentiometry (most popular)
Correction for hypoalbuminemia: total calcium +
(normal albumin - patients albumin) x 0.8 (e.g.,
malignancy)
Normal range: total = 8.8 to 10.3 mg/dL(2.2 to 2.58
mmol/L); ionized = 4.6 to 5.3 mg/dL(1.16 to 1.32
mmol/L)

Increase: serum calcium, absorption of calcium, osteoclast

Hypocalcemia triggers release of PTH
Magnesium

Distribution, function and homeostasis: 99% bone, 1%

ECF; enzymes; cellular energy, nerve conduction,
transfers phosphates, maintains K+ intracellularly;
renal and GIT
Analytical techniques: atomic absorption

spectrophotometry

Range: 0.75 to 0.95 mmol/L

Hormones regulating mineral metabolism
Parathyroid hormone = increases calcium, phosphate

from bone, renal calcium reabsorption, inhibition of

renal phosphate reabsorption, stimulates renal vit D
which increase intestinal absorption of calcium and
phosphates. Over-all effect: increases calcium,
decreases phosphate (chief cells, hyperparathyroid
d/t adenoma most potent hormone in bone
resorption)

Bio-intact PTH = used in uremia and CRF; 20 minute

post-op S/P adenectomy

Parathyroid hormone-related peptide = increased in

carcinomas; same receptors as PTH

Calcitonin = inhibits action of PTH and Vit D

(decreases both calcium and phosphates); increased
in medullary thyroid carcinoma

Vit D metabolites = increase calcium and phosphates

Phosphorus

Distribution and function: organic

phosphates(phospholipids, phosphoproteins) and
inorganic HPO4 and H2PO4; structural unit; oxidative
phosphorylation

Homeostasis: small GIT, kidney, bone

Analytical techniques: ammonium molybdate to form

phosphomolybdate complex

Range: 2.8 to 4.5 md/dL(0.8 to 1.44 mmol/L)

rainwater@mymelody.com || 1st semester, AY 2011-2012

Disorders of Mineral Metabolism

Hypercalcemia
1. Primary hyperparathyroidism = asymptomatic; if
(+) us. Nephrolithiasis (usually due to adenoma)
(Dx late in the disease)
2. Secondary hyperparathyroidism = renal failure
3. Malignancy no PTH ( in PTH-like
substance)

Hypocalcemia
Hypoparathyroidism

Pseudohypoparathyroidism

Chronic renal failure

Early in hyperparathyroidism
Hyperphosphatemia and hypophosphatemia

Hyper = ARF, CRF, intake of phosphates,

acidosis
Hypo = alcohol abuse, antacids, shift of

phosphorous from extracellular into cells

due to sepsis, salicylate poisoning

Hypermagnesemia and hypomagnesemia

Hyper = rare; at risk are elderly, patients

with bowel disorders and renal insufficiency

Hypo = loss of magnesium from GIT and

kidneys; diabetes

Chronic Renal Failure

Bone resorption markers

Pyridium crosslinks (pyridinoline and

deoxypyridinoline) = part of collagen; normal Pyr:
Dpyr ratio is 3 to 3.5: 1. Dpyr is pronounced in
metabolic bone disease

Crosslinked telopeptides = estimating risk of hip

fracture; predicting complications of osteoporosis;
renal osteodystrophy; attached to collagen fragment
Bone formation markers

Alkaline phosphatase= proportional to collagen

formation; high in osteosarcoma and Pagets disease
Osteocalcin= non-collagenous protein of bone;

increased in hyperparathyroidism; decreased in

hypoparathyroidism
Metabolic bone disease

Osteoporosis = decreased organic matrix with normal

mineralization

Osteomalacia and rickets = decreased mineral

content; normal organic matrix
Renal osteodystrophy = decreased organic matrix and

mineral content (hyperparathyroidism,

osteomalacia); d/t retention of phosphate
hypocalcemia increased resorption

Pagets disease = structurally and functionally

abnormal bone; not a metabolic bone disease
bulging bone ; paramyxovirus infection
A. Osteitis Fibrosa Cystica: compact bone is
converted to cancellous bone
osteomalacia end stage: renal
osteodystrophy (spectrum of bone changes)
* Scalloping (thinning of trabeculae)

Normal bone; osteoporotic

Red stain: no scalloping

d/t newly-formed osteoid
Fibrous tissue

A.

Osteomalacia

B.

Renal
Osteodystrophy

B. Chronic Renal Failure

* CC cutting cone
rainwater@mymelody.com || 1st semester, AY 2011-2012